Evaluation of Iohexol Clearance to Estimate Glomerular Filtration Rate in Normal Horse Foals
Estimation of the glomerular filtration rate (GFR), accepted as one of the earliest and most sensitive indicators of renal dysfunction, can be determined in horses using standard techniques
In adult horses and foals, renal dysfunction can occur as a secondary complication to gastrointestinal disorders, dehydration, septicemia, endotoxemia and nephrotoxic drug administration. Measurement of renal function is an important feature not only in the diagnosis, but also in the prognosis and management of renal disease. Commonly used drugs such as phenylbutazone and gentamicin can be highly nephrotoxic under certain conditions. Of particular concern are those drugs, including the aminoglycoside antibiotics, that are eliminated almost exclusively by the kidney. Knowledge of a patients renal status prior to treatment would direct efforts at; 1) restoring kidney function prior to protracted therapy with potentially damaging drugs, 2) adjusting the dose of a life-saving drug based on the magnitude of dysfunction, or 3) selecting a drug that is not dependant on renal function for elimination. such as endogenous or exogenous renal creatinine clearance. Unfortunately, these techniques can be time consuming, dangerous to perform on fractious patients, require trained personnel and are subject to errors most often associated with improper or incomplete urine collection. Recently, tests using iohexol, a radiographic contrast agent, have been developed to estimate the GFR in human beings, dogs and cats with results that have been validated by traditional standards. Most testing protocols require a single bolus injection of iohexol, followed by 2 or 3 blood samples obtained over a few hours. Compared to traditional testing methods, samples are easily and rapidly obtained making the testing procedure less stressful for the patient. A simple method to measure GFR in horses that does not require urine collection, would allow veterinarians in a clinical setting the ability to determine a patient's renal status easily and safely.
The objectives of this study were; 1) model the pharmacokinetic profile of iohexol in horse foals, 2) compare creatinine clearance, an accepted standard for GFR determination in patients, with iohexol clearance, and 3) develop sampling parameters and calculation methods for a practical test, based on iohexol clearance, that compares favorably with creatinine clearance in horse foals.
Iohexol concentration time data were best described using a 3-compartment open model. Mean creatinine clearance (2.17 ml/min/kg) and mean iohexol clearance (2.15 ml/min/kg) showed good agreement. In addition, GFR values for all foals using either method were within published reference ranges for this species. The results of this study indicate that a single intravenous injection of iohexol at a dose of 150 mg/kg, followed by collection of 2 serum samples at 4 and 6 hours post injection can be used to estimate the GFR in healthy horse foals. Mean corrected GFR value (CLpredicted) for 10 foals in this study was 2.15 ml/min/kg.